Effects of dexamethasone on lipopolysaccharide-induced expression of tissue factor, thrombomodulin and protein S on human umbili

Background: Previous reports about the effect of dexamethasone on LPS-induced expression of TF on endothelial cells obtained conflicting results. It was also unclear if dexamethasone could influence LPSinduced expression of TM and PS on endothelial cells. Objective: We re-examined the effects of dexamethasone on LPS-induced expression of TF, TM and PS on HUVEC. Methods: Human umbilical vein endothelial cells in their first to fifth passage were incubated with LPS in serum free medium with or without DEX. After incubation for indicated time, the cells were lysed. The protein levels of TF, TM and PS in the supernatant of the lysates were measured by enzyme-linked immunosorbant assay. Results: The LPS-induced expression of TF in HUVEC was time-dependent and dose-dependent. DEX could counteract the up-regulation effect of LPS (0.1µg/ml) on TF expression. 0.5ìg/ml and 1.0µg/ml DEX made the amount of TF expression decrease from 128.3 ± 25.7 pg/105 cells to 94.9 ± 19.4 pg/105 cells and 98.8 ± 7.8 pg/105 cells respectively (P<0.05). LPS could down-regulate TM expression in HUVEC in a timedependent and dose-dependent manner. The LPS-induced TM expression increased from 0.282±0.014 ng/ 105 cells to 0.409±0.009 ng/105 cells, 0.462±0.017 ng/ 105 cells and 0.362±0.019 ng/105 cells when 0.1µg/ml, 0.5µg/ml and 1.0µg/ml DEX was added respectively. When incubated with LPS (0.1µg/ml), the expression of PS in HUVEC was declining with the prolongation of the incubation time. The level of PS in lysate decreased to 20% and 17% of the control level at 1 hour and 4 hours respectively (P<0.01). DEX could also partially counteract the down-regulation effects of LPS on PS expression. When co-incubated with LPS (0.1µg/ml), DEX (0.5µg/ml) could increase PS expression from13.1 ± 4.8 % per 2×105 cells to 48.5 ± 10.2% per 2×105 cells (P<0.01). Conclusions: LPS could up-regulate the expression of TF and down-regulate the expression of TM and PS in HUVEC in vitro. These effects can be partially counteracted by DEX.